Early Detection Research Network

Chemokine Prostate Cancer Biomarkers

Chemokine Prostate Cancer Biomarkers
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CXCL5 is a pro-angiogenic CXC-type chemokine that is robustly secreted by prostate cancer cells. Tissue microarray analyses have demonstrated that CXCL5 protein expression levels are concordant with prostate tumor progression. Biological assays have demonstrated that CXCL5 promotes both the proliferation and invasiveness/metastasis of prostate cancer cells. CXCL12 is also a pro-angiogenic CXC-type chemokine expressed in bone marrow stroma and tumor endothelium that ‘guides’ invasive prostate cancer cells to establish metastatic tumors in bone. Prostate cancer cells up-regulate protein expression of CXCR4, the CXCL12 receptor, concordantly with prostate tumor progression in response to increasing levels of tumor stromally-secreted CXCL12. Preliminary studies from our laboratory have shown that, among 51 men with low (<10ng/ml) serum PSA values, both serum CXCL5 and serum CXCL12 levels were significantly higher among men who were biopsy-positive compared to those who were biopsy-negative for prostate cancer. These studies also showed that serum CXCL5 levels distinguished cancerous from non-cancerous large volume prostates, whereas CXCL12 accomplished the same for small volume prostates. Based on these preliminary data, we hypothesize that serum, plasma, and urine levels of CXCL5 and CXCL12 can distinguish between men with cancerous or non-cancerous prostates. In order to test this hypothesis, we propose two specific aims intended to assess the robustness and predictive value of these markers.

SPECIFIC AIMS/DELIVERABLES. In order to test this hypothesis, we will accomplish two Specific Aims: Specific Aim 1. Assess the robustness of serum, plasma, or urine measures of CXCL5 and CXCL12. Specific Aim 2. Determine whether serum, plasma, or urine levels of CXCL5 and CXCL12 provide sufficient predictive value for prostate cancer among men with low (<10ng/ml) total serum PSA.
The results of these assays will determine whether statistically significant associations between disease status in the prostate (no disease, BPH, PCa with or without concomitant BPH) and serum, plasma, or urine protein levels for CXCL5 and/or CXCL12 are observed among patients with low but detectable serum PSA. If so, then ROC analyses will determine whether the sensitivity and specificity of these protein levels to ‘predict’ disease status are superior to those of PSA or other similarly evaluated biomarkers as reported in the literature. If so, a larger, multiinstitutional study to validate these findings across a broader patient population will be pursued through collaborative efforts within the NCI-sponsored Early Detection Research Network (EDRN) to validate these findings. Conversely, if no statistically significant associations between disease status in the prostate and serum, plasma, or urine protein levels for CXCL5 and/or CXCL12 are observed, then we will conclude that these proteins do not comprise suitable biomarkers for disease status in the prostate, and that further studies are not warranted.
Aim 1 is completed, Aim 2 is in prcess

There are currently no biomarkers annotated for this protocol.

No datasets are currently associated with this protocol.